Prognostic Factors in Childhood Anaplastic Large Cell Lymphoma: Long Term Results of the International ALCL99 Trial

Lara Mussolin, Marié-Cecilé Le Deley, Elisa Carraro, Christine Damm-Welk, Andishe Attarbaschi, Denise Williams, Amos Burke, Keizo Horibe, Atsuko Nakazawa, Grazyna Wrobel, Georg Mann, Monika Csóka, Anne Uyttebroeck, Rafael Fernández-Delgado Fernández-Delgado Cerdá, Auke Beishuizen, Karin Mellgren, Birgit Burkhardt, Wolfram Klapper, Suzanne D Turner, Emanuele S G D'Amore, Laurence Lamant, Alfred Reiter, Wilhelm Woessmann, Laurence Brugières, Marta Pillon On Behalf Of The European Inter-Group For Childhood Non-Hodgkin Lymphoma Pillon, Lara Mussolin, Marié-Cecilé Le Deley, Elisa Carraro, Christine Damm-Welk, Andishe Attarbaschi, Denise Williams, Amos Burke, Keizo Horibe, Atsuko Nakazawa, Grazyna Wrobel, Georg Mann, Monika Csóka, Anne Uyttebroeck, Rafael Fernández-Delgado Fernández-Delgado Cerdá, Auke Beishuizen, Karin Mellgren, Birgit Burkhardt, Wolfram Klapper, Suzanne D Turner, Emanuele S G D'Amore, Laurence Lamant, Alfred Reiter, Wilhelm Woessmann, Laurence Brugières, Marta Pillon On Behalf Of The European Inter-Group For Childhood Non-Hodgkin Lymphoma Pillon

Abstract

With the aim of describing the long-term follow-up and to define the prognostic role of the clinical/pathological/molecular characteristics at diagnosis for childhood, adolescent and young adults affected by anaplastic large cell lymphoma (ALCL), we analyzed 420 patients aged up to 22 years homogeneously treated within the international ALCL99 trial. The 10-year progression free survival (PFS) was 70% and overall survival was 90%, rare late relapses occurred but no secondary malignancies were reported. Among clinical/pathological characteristics, only patients presenting a small cell/lymphohistiocytic (SC/LH) pattern were independently associated with risk of failure (hazard ratio = 2.49). Analysis of minimal disseminated disease (MDD), available for 162 patients, showed that both SC/LH pattern (hazard ratio = 2.4) and MDD positivity (hazard ratio = 2.15) were significantly associated with risk of failure in multivariate analysis. Considering MDD and SC/LH results, patients were separated into three biological/pathological (bp) risk groups: a high-risk group (bpHR) including MDD-positive patients with SC/LH pattern; a low-risk group (bpLR) including MDD-negative patients without SC/LH pattern; and an intermediate-risk group (bpIR) including remaining patients. The 10-year PFS was 40%, 75% and 86% for bpHR, bpIR and bpLR, respectively (p < 0.0001). These results should be considered in the design of future ALCL trials to tailor individual treatments.

Keywords: ALCL; MDD; childhood; long-term follow-up.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of anaplastic large cell lymphoma (ALCL) patients included in the analysis.
Figure 2
Figure 2
The 10-year overall survival (OS) and progression free survival (PFS) were 90% (SE ± 1%) (a) and 70% (SE ± 2%) (b), respectively, for the full cohort of 420 patients.
Figure 3
Figure 3
The 10-year PFS for the full cohort of 420 patients was 50% (SE ± 5%) in the SC/LH subtype group and 78% (SE ± 2%) in the non-SC/LH group, p < 0.0001, (a); the 10-year PFS in the subset of 162 patients with available MDD data was 53% (SE ± 7%) in SC/LH group and 81% (SE ± 4%) in the non-SC/LH group, p = 0.0006 (b).
Figure 4
Figure 4
The 10-year PFS according to MDD stratification was 62% (SE ± 5%) for the MDD positive patients and 83% (SE ± 4%) for the MDD negative patients, p = 0.001.
Figure 5
Figure 5
The 10-year PFS was 40% (SE ± 8%), 75% (SE ± 5%) and 86% (SE ± 5%) for bpHR (n = 35), bpIR (n = 74) and bpLR (n = 45), respectively (p < 0.0001).

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